Biomedical subjects

R Rickert

Publications and source records attributed to R Rickert.

10 recordsLinked to original sources

PubMed2003

Trans fatty acids (TFA): analysis, occurrence, intake and clinical relevance.

More than one quarter of total daily calories are normally provided by fatty acids which contain at least one double bond. The usual configuration of these double bonds is the cis configuration. Trans fatty acids (TFA) are formed in technological and microbiological processes by isomerization of cis double bonds to trans double bonds. In the 1990s, there was public health concern about epidemiological studies suggesting that TFA increase the risk of coronary heart disease. High intakes of TFA may have an influence on total cholesterol and other blood parameters; but on the other hand there have been a lot of studies which have not been able to confirm these results. TFA are formed in varying amounts during the industrial hydrogenation of vegetable oils and in the first stomach of ruminants. Regular margarines contain varying contents of partially hydrogenated vegetable oils, and therefore of TFA. The main dietary TFA are the trans octadecenoic acids, which contribute to approximately 80-90 % of total TFA content in foods. The predominant isomer of milk fat is trans vaccenic acid, which is directly influenced by ruminant feeding conditions. For a reliable identification and quantification of TFA in foods and other biological matrices it is necessary to use a combination of chromatographic methods (GC-FID, GC-MS, GC-FTIR, Ag superset +-HPLC).

Coronary Disease↗

PubMed2003

Identification and analysis of conjugated linoleic acid isomers (CLA).

CLA are predominantly found in milk, milk products, meat and meat products of ruminants. The distribution of CLA isomers in cheese and/or meat shows one major isomer C18:2 c9t11 with nearly 84% of total CLA. It is estimated that the daily intake of CLA using the German Nutrition Study is 0.35 g/d for women and 0.43 g/d for men.

Animals↗

PubMed2001

Analysis of C-MYC function in normal cells via conditional gene-targeted mutation.

Germline inactivation of c-myc in mice causes embryonic lethality. Therefore, we developed a LoxP/Cre-based conditional mutation approach to test the role of c-myc in mouse embryonic fibroblasts (MEFs) and mature B lymphocytes. Cre expression resulted in reduced proliferation of wild-type MEFs, but c-Myc-deficient MEFs showed a further reduction. In contrast to fibroblasts, Cre expression had no apparent affect on wild-type B cell proliferation. Deletion of both c-Myc genes in B cells led to severely impaired proliferation in response to anti-CD40 plus IL-4. However, treated cells did upregulate several early activation markers but not CD95 or CD95 ligand. We discuss these findings with respect to potential c-Myc functions in proliferation and apoptosis and also discuss potential limitations in the Cre-mediated gene inactivation approach.

Animals↗

PubMed2000

B-cell antigen receptor competence regulates B-lymphocyte selection and survival.

Experimental evidence contradicts the simplistic view that during development all B cells expressing non autoreactive antigen receptors on the cell surface are selected into the mature B-cell pool. While allelic exclusion, clonal selection and affinity maturation continue to define the mainstream notions of B-cell development and selection, new evidence is redefining our understanding of these processes. Receptor editing replaces functional B-cell receptors by secondary immunoglobulin gene rearrangements, a process that can play roles in both immune tolerance and immune response. In addition, editing can rescue cells that would otherwise fail positive selection. We focus here on our studies indicating that the functional competence of the B-cell antigen receptor complex plays a central role in the fate of developing B cells and their antigen receptor genes.

Animals↗

PubMed2000

Hyperreactive onchocerciasis exhibits reduced arachidonate and linoleate levels in serum triglycerides.

The mechanism by which the minority of patients with onchocerciasis exhibiting the hyperreactive (sowda) form of the disease may be able to kill the microfilariae of Onchocerca volvulus is still poorly understood. In this study, the relative amounts of arachidonate and linoleate in serum phospholipids and triglycerides were investigated by gas chromatography both in patients infected with O. volvulus who exhibited either a hyperreactive or a generalized form of onchocerciasis and in persons with no filarial infections. Remarkable differences were observed in the serum triglycerides but not in the phospholipids. In comparison to persons without any filarial infection, significantly lower relative amounts of arachidonate--indicated by elevated triene-tetraene ratios--and of linoleate--indicated by lower diene + tetraene - triene values--were detected in patients with hyperreactive onchocerciasis, and less pronounced differences were found in persons with generalized onchocerciasis. The relationship between reduced amounts of arachidonate and linoleate in serum triglycerides and possible implications on the eicosanoid production in the host-parasite relationship leading to parasite elimination are discussed.

Adolescent↗

PubMed1999

Improved separation of conjugated fatty acid methyl esters by silver ion-high-performance liquid chromatography.

Operating from one to six silver ion-high-performance liquid chromatography (Ag+-HPLC) columns in series progressively improved the resolution of the methyl esters of conjugated linoleic acid (CLA) isomeric mixtures from natural and commercial products. In natural products, the 8 trans, 10 cis-octadecadienoic (18:2) acid was resolved from the more abundant 7 trans, 9 cis-18:2, and the 10 trans, 12 cis-18:2 was separated from the major 9 cis, 11 trans-18:2 peak. In addition, both 11 trans, 13 cis-18:2 and 11 cis, 13 trans-18:2 isomers were found in natural products and were separated; the presence of the latter, 11 cis, 13 trans-18:2, was established in commercial CLA preparations. Three Ag+-HPLC columns in series appeared to be the best compromise to obtain satisfactory resolution of most CLA isomers found in natural products. A single Ag+-HPLC column in series with one of several normal-phase columns did not improve the resolution of CLA isomers as compared to that of the former alone. The 20:2 conjugated fatty acid isomers 11 cis, 13 trans-20:2 and 12 trans, 14 cis-20:2, which were synthesized by alkali isomerization from 11 cis, 14 cis-20:2, eluted in the same region of the Ag+-HPLC chromatogram just before the corresponding geometric CLA isomers. Therefore, CLA isomers will require isolation based on chain length prior to Ag+-HPLC separation. The positions of conjugated double bonds in 20:2 and 18:2 isomers were established by gas chromatography-electron ionization mass spectrometry as their 4,4-dimethyloxazoline derivatives. The double-bond geometry was determined by gas chromatography-direct deposition-Fourier transform infrared spectroscopy and by the Ag+-HPLC relative elution order.

Chromatography, High Pressure Liquid↗

PubMed1996

The dermatologist and managed care.

Because of the economic concerns of the managed care industry, a study was undertaken to demonstrate the economical treatment of cutaneous tumors by dermatologic specialists. The biopsy reports of 300 consecutive tumors were obtained from a suburban medical center pathology department. The diagnostic accuracy and place of treatment of dermatologists and nondermatologists who treated these tumors were compared. This comparison demonstrates a substantial cost saving to third-party carriers, with clear superiority by dermatologists in dealing with this problem.

Cost Savings↗

PubMed1994

M17: a novel gene expressed in germinal centers.

Germinal centers are histologically distinct structures that form within the draining lymphoid tissues following immunization with T cell-dependent antigens. Here, antigen-specific B cells transform the lymphoid follicle into a site of intense B cell proliferation, differentiation and selection. To understand the molecular basis for these cellular events, we sought to isolate germinal center B cell-specific genes using subtractive cDNA libraries derived from FACS-sorted (CD45R/B220+, IgD-, Thy1.2-) lymph node B cells of immunized mice. A novel gene isolated from this library, designated M17, was found to be transcribed in spleen and, to a lesser extent, bone marrow. Strikingly, only PNA+ (germinal center) but not PNA- splenic B cells express M17. Germinal center-specific expression of M17 was confirmed by staining of histological sections of spleen with an antiserum raised against a glutathione-S-transferase-M17 fusion protein. The M17 gene comprises four exons spanning 13.2 kb, and encodes a 25 kDa cytoplasmic protein of 159 amino acids. Analysis of the amino acid sequence revealed the presence of a possible lipid binding domain and multiple potential phosphorylation sites, including a tyrosine-based activation motif. We speculate that M17 may be a signaling molecule involved in the transduction of signals from the cell surface to the cytoplasm.

Amino Acid Sequence↗

PubMed1993

Low frequencies of somatic mutation in two expressed V kappa genes: unequal distribution of mutation in 5' and 3' flanking regions.

Somatic mutation of antibody variable region genes is a hallmark of secondary responses. Most often the coexpressed VH and V kappa genes of a B cell mutate at nearly equal rates. We have previously identified hybridomas from two B cell clones that exhibited > 10-fold lower frequency of mutation in their expressed V kappa 12 or V kappa 1A genes relative to their coexpressed VH genes. To gain insight into the mechanism(s) responsible for this low frequency V kappa mutation, we determined the frequency of mutation in non-coding flanking DNA from multiple members of each clone. We find a low frequency of mutation in the 5' (4/700) and 3' (1/670) non-coding regions of the expressed V kappa 1A genes consistent with the low frequency of coding region mutation. In contrast, the distribution and frequency of mutation surrounding the expressed V kappa 12.37 gene are unusual. Among the six members of this clone there are 31 mutations 3' (31/2100 bp) and no mutations 5' (0/2010 bp) of the V kappa exon. This V kappa exon has acquired mutations that are intermediate in number to its flanking regions and are significantly skewed in distribution to the 3' end. None of the 31 3' mutations are shared by two or more members of this clone, indicating that they all occurred late in clonal expansion. These results raise the possibility that some V kappa genes may lack functional cis-regulatory elements which direct V kappa coding region mutation.

Animals↗

PubMed1990

The BALB/c secondary response to the Sb site of influenza virus hemagglutinin. Nonrandom silent mutation and unequal numbers of VH and Vk mutations.

We have determined the nucleotide sequences of the expressed VH and Vk genes from 13 secondary (2 degrees) hemagglutinin (HA) (Sb) specific hybridomas derived from a single mouse. These antibodies share an Id, H37-68 (68Id) that dominates the 2 degrees HA(Sb) response in this mouse, but is rare or absent from 2 degrees responses of other mice. We find that these antibodies derive from five clones. The H chains of these antibodies are encoded by a single VH gene joined to a variety of DH and JH genes. The length of complementarity-determining region (CDR) 3 and sequence of the D-J junction are restricted, suggesting selection on CDR3 of the H chain. The L chains are more diverse. In the presented examples, they are encoded by the Vk21C and Vk21E genes and a Vk9 gene, and are joined to Jk1, 2, or 4. Each antibody is extensively mutated. The nature and distribution of the mutations suggests that 68Id-producing cells have been selected by Ag, although there are differences regarding the domain (VH, Vk, or both) in which mutations were selected. The implications of these findings on the idiosyncratic nature of the 68Id antibody response to HA(Sb) are discussed. There are two unusual characteristics regarding somatic mutation in these hybridomas. Whereas the expressed VH and Vk21 genes appear to have accumulated mutations at a high rate (1 to 1.5 x 10(-3)/base pairs/division, the expressed Vk9 genes appear to have accumulated mutations at a 5 to 15-fold lower rate than the expressed VH genes in the same cells. There is also a surprisingly high number of parallel silent somatic mutations in the VH genes, of which all but one are clustered to a 28-bp region in framework region 2 and CDR 2-encoding segments. The probability that this could have occurred by a random mutational process is essentially zero.

Amino Acid Sequence↗